UC San Diego

Neural circuits represent and process information using large numbers of component neurons. In this thesis, I describe the current theories of how information is processed by nervous systems, biophysical models of the basic mechanisms of population coding, and experimental techniques and computational algorithms to collect and synthesize the data necessary to understand neural computation in simple nervous systems. The leech nervous system is an ideal system for study, because it is readily accessible and consists of core neural structure, the ganglion, built of only a few hundred neurons. Even though this system is simple compared to mammalian nervous systems, it is still remarkably complex. To understand this complexity and make sense of the patterns of neurons, large-scale recordings of neural activity are required. We have developed a new Voltage-Sensitive Dye to record from a significant fraction of the nervous system simultaneously during behavioral states. This type of large-scale data presents entirely new challenges to overcome, and we developed computational tools to visualize and stitch-together these large-scale recordings. By imaging from a ganglion in several animals and recording neural responses during several different behaviors, we have developed a system for scalable and rapid identification of dozens of individual neurons. With these tools and techniques, we have mapped out the activity of a significant fraction of the leech's nervous system and have identified dozens of novel cells. Many of these cells are part of two canonical networks in the leech nervous system: the swim and preparatory networks. We further show that the preparatory network is mediated by the S cell, and we use computationally guided electrophysiology to target and verify that the S cell drives the activity of other cells in the preparatory network. These tools enable us to study the nervous system at scale for the first time, and we have mapped out the roles of a significant fraction of the neurons during the production of behaviors. These are just the first steps necessary to build a complete picture of how leech neurons produce behavior and make decisions.